gelareh vahabzadeh

 Borderline personality disorder (BPD) has been considered a psychiatric disorder, the effective pharmacological treatments for which have not been well established.

 This study aimed to assess the efficacy of memantine (10 mg/day) in reducing BPD severity and cognitive impairment.

 The BPD patients diagnosed by psychologists were included and divided into the placebo (n = 19) and memantine (n = 20) groups. Included participants were randomized, double-blinded, and stabilized on the medication and psychotherapy for at least four weeks. The patients in the memantine group received oral memantine (10 mg/day) for four weeks. The severity of BPD was assessed by a self-reported questionnaire named Borderline Evaluation of Severity Over Time (BEST). Moreover, the Wisconsin test was carried out to assess executive function.

 The mean score of the BEST test significantly decreased in week eight post-treatment in the memantine group. In addition, a significant decrease in this score was indicated in the memantine group compared to the placebo group in week eight. The mean total score of the BEST test was not significantly different before and after the placebo administration. There was no significant difference in the Wisconsin subscales, including the number of wrong answers and categories achieved after memantine or placebo administration. Perseverative errors rose after the administration of memantine. Adverse side effects did not occur in any of the participants.

 Our findings suggested the potential therapeutic effects of memantine for BPD. Furthermore, we found that a low dose of meantime might be preferable to prevent the side effects.

 Epilepsy is one of the most important diseases of the central nervous system, for which has no definitive treatment. Neurotrophic factors increase the survival of nerve cells and improve the treatment of neurological diseases. Identifying factors that affect the increase of neurotrophins in the brain is an important goal for brain health and function.

 This study aimed to investigate the effectiveness of exercise on neurotrophic factors by influencing the expression of vanilloid receptor type 1 (TRPV1).

 Convulsions were induced by injecting pentylenetetrazol (PTZ; 35 mg/kg) five hours after exercise. Animals were divided into five groups: sham (Sham), seizure (PTZ), exercise (EX), exercise with seizure induction (EX+PTZ), and exercise before seizure induction (EX-PTZ). The exercise was 30 minutes of forced running on a treadmill, five days a week for four weeks.

 The average percentage of NGF cells in the exercise groups (EX), exercise with seizure induction (EX+PTZ), and exercise before seizure induction (EX-PTZ), and GDNF in the exercise group with seizure induction (EX+PTZ) had a significant increase compared to the seizure group (PTZ). Also, TRPV1 activity in exercise groups (EX), exercise with seizure induction (EX+PTZ), and exercise before seizure induction (EX-PTZ) showed a significant increase compared to the seizure group (PTZ).

 Our findings suggested the possible antiepileptic and antiepileptogenesis effects of exercise through activation of neurotrophic factors and TRPV1 modulation.

 Osteosarcoma (also called osteogenic sarcoma) is the most common type of cancer that starts in the bones. It is a malignant mesenchymal cell tumour, characterized by pleomorphic spindle-shaped cells, capable of producing an osteoid matrix. Tumour cells metastasize primarily via the haematogenous route. This disease is very aggressive and the tumor formed is fixed, hard and irregular. The cancer cells in these tumors look like early forms of bone cells that normally help make new bone tissue, but the bone tissue in an osteosarcoma is not as strong as that in normal bones. Overall, osteosarcoma is a rare disease, however, children and teens are the most commonly affected age group, but osteosarcoma can develop at any age. Although this disease occurs sporadically, approximately 70% of tumor specimens show an abnormality in the chromosome. Moreover, regulation of cell cycle has been reported to demonstrate inherited defects in some cases. The incidence of osteosarcoma is bimodal. The first peak occurs at the ages of puberty, implying the ages of 15 to 19 in boys and the ages of 10 to 14 in girls. The second peak occurs in the elderly with the age of 75 years. Noteworthy, osteosarcoma is rare before the age of 5. With the application of multimodal chemotherapy, disease-free survival of patients with high-grade osteosarcoma has been improved to more than 60% compared to 10–20% which was reachable with the surgery as the only therapeutic approach. At present, treatment of osteosarcoma is a combination of surgery and chemotherapy both before and after the surgery. Additionally, the use of common chemotherapeutic agents such as high-dose methotrexate, cisplatin, doxorubicin and/or etoposide and ifosfamide frequently causes both acute and long-term toxicity. Although several chemotherapy regimens have been applied in the past 20 years, survival rates of patients are still not satisfying and no practical targeted therapy is discovered. Therefore, it is important to investigate different therapeutic methods and anti-tumor agents in order to find an approach that provides a higher survival rate. Flavonoids possess several biological and pharmacological activities. In addition, flavonoids have the advantage of being less toxic and can be prescribed for an extended duration. Therefore, various plant-derived flavonoids use as drugs have been reported as a modulator for chronic inflammation caused by virus infection and other diseases, such as human papillomavirus, hepatitis virus, SARS-CoV-2, autoimmune disease, type 2 diabetes, cardiovascular diseases, Alzheimer’s disease, Parkinson’s disease, and cancer. Quercetin is a naturally occurring polyphenolic flavonoid, whose chemical name is 3,3′,4′,5,7-Pentahydroxyflavone (C15H10O7), can be found in a wide range of daily foods, such as grains, fruits, and vegetables and in higher levels in capers, buckwheat seeds, radish, onions, apples, red leaf lettuce, asparagus, nuts, and teas. It is reported that oral administration of 1 g quercetin per day is safe and is absorbed up to 60%. Quercetin has a high ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) molecules; therefore, exhibiting beneficial effects in preventing obesity, diabetes, cardiovascular diseases, and inflammation. Furthermore, quercetin is indicated to exert various anti-tumor effects both in vitro and in vivo against several cancers, such as ovarian cancer, colorectal cancer, lymphoma, gastric cancer, and breast cancer. On the other hand, the high toxic effect of quercetin against cancer cells is accompanied with little or no side effects or harm to normal cells. Its wide accessibility, efficacy, and a broad range of activity, and low toxicity as compared with other examined compounds, make it an attractive chemical in the fight against diseases including cancer. It has been recognized and employed as an alternative drug in treating different cancers alone or in combination with other chemotherapeutic drugs. NO is a free radical that regulates several physiological functions and is formed by the conversion of L-arginine to L-citrulline by nitric oxide synthases (NOS). NO is a dual molecule that can have a tumor-protecting or stimulating effect, depending on its local concentration. Certain reports demonstrated a cytotoxic role of NO; others presented a protective role. Many investigations have shown that quercetin has anti-inflammatory activity that pulls out the nitric oxide, catalase, and cytokines, specifically TNF-α, IL-β, and IL-6, which are inflammatory mediators. Therefore, we tried to elucidate the influence of quercetin in order to suggest a new candidate for the treatment of this cancer, on in vitro NO production from Saos2 osteosarcoma cell line

After 24 hours of culture of Saos2 cells in 96-well plates, different concentrations of quercetin were added to the wells for 72 hours. Cell viability was measured using the colorimetric MTT assay. Briefly, cells were incubated with 0.5mg/mL MTT in DMEM at 37 ºC under 5 % CO2 for 3 h. The blue formazan reduction product, which is generated by the action of the succinate dehydrogenase on the dye only in living cells, was dissolved in 100µL DMSO, and its absorbance was read at 570nm using a Dynex MMX microplate reader. The level of nitrite as an indicator of NO production in the culture medium was measured using modified Griess reagent. In brief, after the experiment, the medium in each well was removed and centrifuged at 10,000 g for 10 min at 20 ºC. Then, 100 µL of the supernatant was mixed with an equal volume of Griess reagent at room temperature for 10 min, and the absorbance was measured at 540 nm using a microplate reader. The nitrite concentration was determined from a sodium nitrite standard curve.
The data were analyzed by one-way ANOVA and P < 0.05 was considered statistically significant.

The results of this study showed that quercetin can decrease the percentage of cell viability of Saos2 cells compared to the control group. The best effective dose is 120 μM. Also, the data showed that quercetin in all concentrations was able to reduce the production of NO levels in Saos2 cells and the best effective concentration is 120 μM.

In this study, it was found that quercetin was able to reduce the viability of Saos2 cells, and part of its effects could be mediated partially by a decrease in NO production. However, further studies are needed on this natural compound.

In vitro obtaining oocytes can be an appropriate alternative for patients with gonadal insufficiency or cancer survivors. The purpose of the current research was isolating stem cells from ovarian cortical tissue as well as evaluating the effectiveness of follicle stimulating hormone (FSH), basic fibroblast growth factor (bFGF), and neurotrophin 3 (NT3) in differentiating to oocyte-like cells.

A human ovary was dissected and cortical tissue pieces were cultured for cell isolation. Isolated cells were divided into 8 groups (3 cases in each group) of control, FSH, NT3, bFGF, FSH+NT3, FSH+bFGF, NT3+bFGF, and FSH+NT3+ bFGF. Pluripotency specific gene (OCT4-A and Nanog), initial germ cells (c-KIT and VASA) and PF growth initiators (GDF-9 and Lhx-8) were evaluated by qRT-PCR. Experiments were performed in triplicate and there were 3 samples in each group. The results were analyzed using one-way ANOVA and p-value less than 0.05 was considered statistically significant.

Flow cytometry results showed that cells isolated from the ovarian cortex expressed markers of pluripotency. The results showed that the expression of Nanog, OCT4, GDF-9 and VASA was significantly increased in FSH+NT3 group, while treatment with bFGF caused significant expression of c-KIT and Lhx-8 (p<0.05). Also, according to the results, isolated cells treated with NT3 significantly increased c-KIT expression.

According to our results, the ovarian cortex cells could be differentiated into primordial follicles if treated with the proper combination of FSH, bFGF, and NT3. These findings provided a new perspective for the future of in vitro gamete proudest.

In the present study, we investigated the effects of noscapine (0.5-2 µM), an alkaloid from the opium poppy(Papaver somniferum), on primary murine cortical neurons exposed to 60 min oxygen–glucose deprivation (OGD) in the presence of 5 µM BD-1047, a selective sigma-1 receptor antagonist. The experiments were performed on cortical neurons after 11–16 days of culture. To initiate oxygen–glucose deprivation, the culture medium was transferred to glucose-free DMEM, and placed in a humidified incubation chamber containing a mixture of 95% N2 and 5% CO2 at 37 °C for 60 min. In order to explore the effect on neurons under oxygen–glucose deprivation in this condition, some cultures were pretreated with noscapine and BD1047 together, 24 h prior to OGD followed by 24 h recovery. Cell viability, nitric oxide (NO) production and intracellular calcium concentration ([Ca2+]i) levels were evaluated by MTT assay, the modified Griess method, and Fura-2, respectively. Pretreatment of the cultures with noscapine in the presence of BD1047 significantly increased cell viability and decreased NO generation in a dose-dependent manner compared to BD1047 alone. Pretreatment with 2 μM noscapine and BD-1047 was shown to decrease the rise in [Ca2+]i induced by sodium azide (NaN3) and glucose deprivation. We concluded that noscapine in the presence of BD1047 could protect primary cortical neurons after oxygen–glucose deprivation-induced cell injury but this effect was not complete. Our results indicate that neuroprotective effects of noscapine could be mediated partially through activation of sigma-1 receptor and by decreasing NO production and [Ca2+]i levels.

BackgroundMethylphenidate (MPH) is commonly prescribed for children who have been diagnosed with attention deficit hyperactivity disorder (ADHD); however, the action mechanisms of methylphenidate have not been fully elucidated. Studies have shown a relationship between apoptosis signaling pathways and psychiatric disorders, as well as therapeutic targets for such disorders. So, we examined the effects of chronic methylphenidate administration on the brain of mice.
Materials and MethodsAnimals were administered MPH at doses of 2, 5 and 10 mg/kg for 60 days. At the age of three months and in estrous phase, brian tissues were removed and washed in cold phosphate-buffered saline and some of them were frozen at -80oC for Western blot analysis. We measured the levels of pro-apoptotic protein, Bax and anti-apoptoticprotein, Bcl-2, in the brain of neonate female Balb/c mice. The rest of the brains were fixed in formalin (10% phosphate-buffered, pH = 7.4). Then samples were embedded in paraffin according to routine histologic procedures.
Our results showed that MPH with a dose of 10 mg/kg causes a considerable increase in the level of the Bax protein as compared with other groups. In contrast, in the partial cortex of female mice under treatment with high dose of MPH (10 mg/kg) could less Bcl2 levels as compared with 5 mg/kg MPH. However, 5 mg/kg MPH have a significant effect on Bcl2 levels compare with each of mentioned doses (PConclusionOur results suggest that long-term administration of MPH in the mouse brain had influence on the cascade of apoptosis and its effects, depends on dose rate.

phytoestrogens are some plant compounds with estrogenic biological effects which are found in many nutritional sources as soybean, flaxseed and sesame. Vitex agnus-castus, also called Vitex, owns phytoestrogenic properties. Studies have showed that phytoestrogens have different impacts on the gestation process and reproduction indices. The present study is aimed at investigating the effects of Vitex extract on the gestation indices in the male rat as well as studying its histological properties in the rat's testicles.
The hydro-alcoholic extract of Vitex (in three doses of 165, 265 and 365 mg/kg), vehicle (normal saline) and the hydro-alcoholic powder of soybean (120 mg/kg) were respectively given to understudy, vehicle and positive control groups for 49 days. After weighing the rats in the 1st and 49th days, the blood samples of all groups were taken and tested for estradiol levels, testosterones, FSH and LH. Moreover, such reproductive indices as sperm count, sperm motion, and prostate and testicle weight were studied and samples were collected for histological studies.
Prescription of the hydro-alcoholic extract of Vitex (in three doses of 165, 265 and 365 mg/kg) did not significantly change the rats weight (P-value= 0.06). Hormonal studies significantly reduced the progesterone, LH and FSH compared to vehicle group (P-value

Excessive activation of NMDA receptors in ischemic injury as well as reduction of GABAergic system leads to discrepancies of ionic homeostasis and neuronal death. The aim of the present study was to evaluate the effect of different concentrations of stiripentol (0.01, 0.1, 1, 5, 10, 30 µM) as a GABAA receptor agonist on primary cortical culture of mice on 4 h oxygen-glucose deprivation (OGD).
After 24h of incubation of neuronal cells with stiripentol, the cells were transferred to glucose-free DMEM (Dulbecco's Modified Eagle Medium) and were exposed to 4h hypoxia in a small anaerobic chamber and incubated in standard condition for 24h. Cell viability was evaluated by MTT assay.
The results showed that different concentrations of stiripentol could increase the cell viability after 4h OGD Recovery (OGD/R). However, the protective effect of stiripentol was lower than the control group (the cells did not expose to OGD/R).
Our results indicated that stiripentol could be a potential drug for treatment of brain ischemic condition. However, additional studies are needed to evaluate the mechanims of strripentol effect.

In the present work we set out to investigate the neuroprotective effects of noscapine (0.5-2 µM) in presence of D-glucose on primary murine foetal cortical neurons after oxygen–glucose deprivation/24 hrs recovery. Cell viability, nitric oxide production and intracellular calcium ([ca2]i) levels were evaluated by MTT assay, the modified Griess method and Fura-2 respectively. 25 and 100 mM D-glucose could, in a concentration dependent manner, improve cell viability and decrease NO production and [ca2]i level in neuronal cells after ischemic insult. Moreover, pre-incubation of cells with noscapine, noticeably enhanced protective effects of 25 and 100 mM D-glucose compared to similar conditions without noscapine pre-treatment. In fact, noscapine attenuated NO production in a dose-dependent fashion, after 30 minutes (min) OGD, during high-glucose (HG) condition in cortical neurons. Pretreatment with 2 μM noscapine and 25 or 100 mM D-glucose, was shown to decrease the rise in [ca2]i induced by Sodium azide/glucose deprivation (chemical OGD) model. These effects were more pronounced than that of 25 or 100 mM D-glucose alone.
The present study demonstrated that the neuroprotective effects of HG after an ischemic insult were augmented by pre-treatment with noscapine. Our results also suggested that the neuroprotection offered by both HG and noscapine involve attenuation of NO production and [ca2]i levels stimulated by the experimental ischemia in cortical neurons.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with unknown etiology. Neurotrophins are polypeptides belonging to the neurotrophic factor family. Neurotrophins mediate cell survival and proliferation in the nervous system. In this study, we determined the production of various neurotrophins, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and glial cell-derived neurotrophic factor (GDNF) in Cuprizone model of demyelination.
In order to induce demyelination, animals were treated by Cuprizone. The mice were divided into three groups. The first group was treated by Cuprizone for 5 weeks. The second group was treated by Cuprizone for 5 weeks and normal diet for 1 week. The third (control) group received normal diet for 6 weeks. After the mice were sacrificed, cerebral corpus callosum was removed and evaluated for expression of neurotrophic factors by real time PCR and histological evaluation.
After five weeks, we detected a significant increase of BDNF and GDNF compared to the control group. No changes were observed in CNTF expression. After six weeks, expression of BDNF and GDNF were decreased but they had still higher levels compared to control group.
This study suggests that neurotrophins may play a role in pathogenesis of MS.

Heparin and enoxaparin possess anti-inflammatory properties. We compared the effects of these drugs on inflammatory biomarkers in patients with ST-segment Elevated Myocardial Infarction (STEMI). Thirty four patients with STEMI randomly separated in two groups and received standard doses of heparin and enoxaparin. The serum concentration of Serum Amyloid A (SAA), C-Reactive Protein (CRP), Interleukin (IL)-6, ferritin and Myeloperoxidase(MPO) were measured at baseline, 12, 24 and 48 hours after drug administration. Serum concentrations of SAA (P: 0.02), CRP (P: 0.02) and ferritin (P: 0.01) significantly reduced in heparin group during measurements compared to baseline, circulating levels of IL-6 (P: 0.002), SAA (P: 0.009), CRP (P: 0.01) were significantly decreased in enoxaparin group. The overall difference in inflammatory biomarkers between heparin and enoxaparin group was not significant. Both heparin and enoxaparine reduced serum levels of inflammatory biomarkers in patients with STEMI. This effect may provide additional clinical benefit of these drugs in the treatment of STEMI patients.